Neurotransmitter receptors on microglia

Microglia are the intrinsic immune cells of the brain and express chemokine and cytokine receptors that interact with the peripheral immune cells. Recent studies have indicated that microglia also respond to the brain's classical signalling substances, the neurotransmitters. Here, we review the evidence for the expression of neurotransmitter receptors on microglia and the consequences of this receptor activation for microglial behaviour. It is evident that neurotransmitters instruct microglia to perform distinct types of responses, such as triggering an inflammatory cascade or acquiring a neuroprotective phenotype. Understanding how microglia respond to different neurotransmitters will thus have important implications for controlling the reactivity of these cells in acute injury, as well as for treating chronic neurodegenerative diseases

Validation of home oxygen saturations as a marker of clinical deterioration in patients with suspected COVID-19

Background The early identification of deterioration in suspected COVID-19 patients managed at home enables a more timely clinical intervention, which is likely to translate into improved outcomes. We undertook an analysis of COVID-19 patients conveyed by ambulance to hospital to investigate how oxygen saturation and measurements of other vital signs correlate to patient outcomes, to ascertain if clinical deterioration can be predicted with simple community physiological monitoring. Methods A retrospective analysis of routinely collected clinical data relating to patients conveyed to hospital by ambulance was undertaken. We used descriptive statistics and predictive analytics to investigate how vital signs, measured at home by ambulance staff from the South Central Ambulance Service, correlate to patient outcomes. Information on patient comorbidities was obtained by linking the recorded vital sign measurements to the patient's electronic health record at the Hampshire Hospitals NHS Foundation Trust. ROC analysis was performed using cross-validation to evaluate, in a retrospective fashion, the efficacy of different variables in predicting patient outcomes. Results We identified 1,080 adults with a COVID-19 diagnosis who were conveyed by ambulance to either Basingstoke & North Hampshire Hospital or the Royal Hampshire County Hospital (Winchester) between March 1st and July 31st and whose diagnosis was clinically confirmed at hospital discharge. Vital signs measured by ambulance staff at first point of contact in the community correlated with patient short-term mortality or ICU admission. Oxygen saturations were the most predictive of mortality or ICU admission (AUROC 0.772 (95 % CI: 0.712-0.833)), followed by the NEWS2 score (AUROC 0.715 (95 % CI: 0.670-0.760), patient age (AUROC 0.690 (95 % CI: 0.642-0.737)), and respiration rate (AUROC 0.662 (95 % CI: 0.599-0.729)). Combining age with the NEWS2 score (AUROC 0.771 (95 % CI: 0.718-0.824)) or the measured oxygen saturation (AUROC 0.820 (95 % CI: 0.785-0.854)) increased the predictive ability but did not reach significance. Conclusions Initial oxygen saturation measurements (on air) for confirmed COVID-19 patients conveyed by ambulance correlated with short-term (30-day) patient mortality or ICU admission, AUROC: 0.772 (95% CI: 0.712-0.833). We found that even small deflections in oxygen saturations of 1-2% below 96% confer an increased mortality risk in those with confirmed COVID at their initial community assessments

Central masked adjudication of stroke diagnosis at trial entry offered no advantage over diagnosis by local clinicians: Secondary analysis and simulation

Background: Central adjudication of stroke type is commonly implemented in large multicentre clinical trials. We investigated the effect of central adjudication of diagnosis of stroke type at trial entry in the Efficacy of Nitric Oxide in Stroke (ENOS) trial. Methods: ENOS recruited patients with acute ischaemic or haemorrhagic stroke, and diagnostic adjudication was carried out using cranial scans. For this study, diagnoses made by local site clinicians were compared with those by central, masked adjudicators using kappa statistics. The trial primary analysis and subgroup analysis by stroke type were re-analysed using stroke diagnosis made by local clinicians, and simulations were used to assess the impact of increased non-differential misclassification and subgroup effects. Results: Agreement on stroke type (Ischaemic, Intracerebral Haemorrhage, Unknown stroke type, No-stroke) was high (κ = 0.92). Adjudication of stroke type had no impact on the primary outcome or subgroup analysis by stroke type. With misclassification increased to 10 times the level observed in ENOS and a simulated subgroup effect present, adjudication would have affected trial conclusions. Conclusions: Stroke type at trial entry was diagnosed accurately by local clinicians in ENOS. Adjudication of stroke type by central adjudicators had no measurable effect on trial conclusions. Diagnostic adjudication may be important if diagnosis is complex and a treatment-diagnosis interaction is expected. © 201